Haemophilus influenzae type b is the leading cause of bacterial meningitis in infants and children. It is also a major cause of septicemia, septic arthritis pneumonia and epiglottitis. Pneumococcus type 6A (Pn6A) is a major cause of otitis media and the most frequent pneumococcal type causing meningitis and pneumonia. Anticapsular antibodies are protective against disease but their induction by vaccines composed of purified capsular polysaccharide is hampered by both their poor immunogenicity in this young age group and lack of anamestic response. In contract, conjugates composed these polysaccharides covalently bound to tetanus toxoid were immunogenic in laboratrory mice and infant rhesus; and this response could be boosted by further injections. Simultaneous injections of both conjugates with tetanus toxid or with DTP enhanced the response to both polysaccharides. Adult volunteers were immunized 2 times at 3 week intervals with conjugates composed of H. influenzae type b, the closely related E. coli K100 or Pn6A polysaccharides and tetanus toxoid in the following schedule: Group 1: Hib-TT, 50 Mug/dose; Group 2: Pn6A, 50 Mug/dose; Group 3: Hib-TT, 50 Mug + Pn6A, 50 Mug; group 4: Hib-TT, 50 Mug + K100-TT, 50 Mug; Group 5: Hib-TT, 100 Mug. Local and systemic reactions were noted in about half of the vaccinees following the first immunization, especially in the groups that received the high dose (100 Mug total) vaccines. No serious reactions occurred. 50 Mug Hib TT alone was given to groups 3, 4, and 5 for the 2nd immunization. The antibody responses, assayed by RIA and ELISA, showed marked increases in antibody levels in Greater than 95% of the volunteers. Hib and TT antibodies increased 10-1000 fold, Pn6A; 5-20 fold. A maximal response occurred in most volunteers after the 1st injection, with no booster response after the 2nd. No relation was found between the preimmune level of antibodies to the vaccine components or the rate of antibody rise to the side effects of the vaccines.